Abstract
The objective of this work was to demonstrate the role of COX-2 enzyme at the vascular in experimental model of metabolic syndrome. SHR male WKY rats were employed; they were distributed in 8 groups (n = 8 each): control (W); W + L: WKY rats receiving 20 mg/kg of lumiracoxib by intraesophageal administration; SHR; SHR + L: SHR + 20 mg/kg of lumiracoxib by intraesophageal administration; Fructose-Fed Rats (FFR): WKY rats receiving 10% (w/v) fructose solution in drinking water during all 12 weeks; FFR + L: FFR + 20 mg/kg of lumiracoxib by intraesophageal administration; Fructose-Fed Hypertensive Rats (FFHR): SHR receiving 10% (w/v) fructose solution in drinking water during all 12 weeks; and FFHR + L: FFHR + 20 mg/kg of lumiracoxib by intraesophageal administration. Metabolic variables, blood pressure, morphometric variables, and oxidative stress variables were evaluated; also MMP-2 and MMP-9 (collagenases), VCAM-1, and NF-κB by Westernblot or IFI were evaluated. FFHR presented all variables of metabolic syndrome; there was also an increase in oxidative stress variables; vascular remodeling and left ventricular hypertrophy were evidenced along with a significant increase in the expression of the mentioned proinflammatory molecules and increased activity and expression of collagenase. Lumiracoxib was able to reverse vascular remodeling changes and inflammation, demonstrating the involvement of COX-2 in the pathophysiology of vascular remodeling in this experimental model.
Highlights
The traditional view of atherosclerosis as a lipid storage disease falls apart against the large and growing evidence that inflammation is at the center of all stages of the disease, from the initial injury until the final stage of thrombotic complications that compromise blood flow
Fructose-Fed Rats (FFR) and Fructose-Fed Hypertensive Rats (FFHR) groups are characterized as a model of metabolic syndrome according to the increase of the Homeostasis model assessment (HOMA) index, fasting blood glucose, triglycerides, decreased HDL-cholesterol, and arterial hypertension
The most important finding of this study was the demonstration that ciclioxigenasa-2 participates in the cardiovascular remodeling associated with metabolic syndrome and the reversal of this syndrome after chronic treatment with a specific antagonist, lumiracoxib (L)
Summary
The traditional view of atherosclerosis as a lipid storage disease falls apart against the large and growing evidence that inflammation is at the center of all stages of the disease, from the initial injury until the final stage of thrombotic complications that compromise blood flow. Advances in the understanding of vascular inflammation have resulted in a radical change in the way vascular diseases are approached. With increased awareness of the active role of the vessel and its complex interactions with cytokines and immune cells, this concept unites disorders previously thought be different. Understanding atherosclerosis as a vascular inflammation disease is the basis of a new approach for risk stratification and treatment [1]. MMPs are induced by cytokines and by cell-cell and cellmatrix interactions. Examples of the increased presence of MMPs in clinical pathology are the SCA, in the vulnerable region of the plaque [2]. Exposure to oxidized low density lipoproteins (ox-LDL) or TNF-α induces the expression of MT3-MMP, an MMP expressed in the atherosclerotic plaque of macrophages [3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
